A Targeted, Real-Time, Technology-Supported Intervention for Patients With Alcohol Use Disorder on Disulfiram

Excessive alcohol use is associated with a host of economic and health problems, with an
estimated annual burden of over $249 billion. One-third of the population will meet
diagnostic criteria for alcohol use disorder (AUD) in their lifetime. Among those who become
abstinent, relapse rates are high, particularly in the first 90 days of sobriety.
Pharmacotherapy continues to be an effective treatment approach. Several FDA-approved
medication-assisted therapies are used, commonly disulfiram (Antabuse) 5. Disulfiram acts as
a "psychological deterrent" and causes physiological reactions when taken with alcohol.
Despite demonstrated efficacy for decreasing relapse, disulfiram is underutilized, primarily
because of the supervision and monitoring required for its most efficacious use. In addition,
disulfiram adherence rates are low. Reasons for non-adherence may be non-deliberate (i.e.,
forgetfulness), but often are deliberate (i.e., contemplating or planning a relapse to
alcohol use). Indeed, individuals who discontinue disulfiram relapse approximately 50 hours
after a missed dose 4. Thus, disulfiram discontinuation may be a proxy for a return to
drinking. Identifying this window before relapse, through medication monitoring and
implementing a just-in-time intervention, may reduce risk of relapse.

Previous methods used to monitor adherence have been subject to self-report bias, have been
constrained by the need for observer reports, have measured prescription refills as a proxy
for adherence, or have relied on participant attendance at later assessment sessions to
collect data. Technological advances now offer the opportunity to objectively measure
adherence in real time through opening of the medication bottle. The Wisepill device is an
electronic medication event monitoring systems that can pair real-time monitoring with a
triggered text message (Short Message Service; SMS) when doses are late. Studies utilizing
Wisepill plus medication reminder SMS messages find increased adherence to antiretroviral or
diabetic therapy. Though the capability exists, potentially therapeutic SMS messages paired
with Wisepill objective monitoring have yet to tested. Given that disulfram non-adherence can
signify a potentially critical clinical concern (i.e., impending relapse), the delivery of a
tailored, relapse prevention-focused, just-in-time message soon after a disulfiram dose has
been missed could have a significant impact on AUD treatment outcomes. Indeed, previous
research suggests that supportive and relapse prevention/coping skills SMS message
interventions are effective in reducing rates of alcohol use. The investigators propose to
develop an intervention capitalizing on the Wisepill technology to pair real-time medication
monitoring with tailored (a) real-time triggered reminders, (b) real-time abstinence support,
and (c) relapse prevention SMS texts for individuals with AUD being treated with disulfram.

PRIMARY AIMS

1. To develop a 12-week Wisepill+SMS intervention for individuals in intensive outpatient
alcohol treatment who are prescribed disulfram. This will include: 1) an in-person Wisepill
orientation session to introduce the device and generate relapse prevention messages that can
be later delivered during non-adherent windows; 2) use of the Wisepill device during the
intensive treatment program and after discharge; and 3) three forms of tailored SMS messages
paired with Wisepill device use: a) supportive messages with medication compliance, b)
reminder messages for early non-adherence (e.g., 1 hour late) and c) relapse-prevention
messages after longer periods of non-adherence (e.g., several hours).

1a. The investigators will conduct 4 focus groups (total n=20) with patients previously (2
groups) and currently (2 groups) prescribed disulfram to help identify barriers to the
Wisepill+SMS intervention, inform the types of SMS messages to be delivered, and determine
strengths and limitations of the proposed intervention.

1b. The investigators will modify and finalize the Wisepill+SMS intervention, based on data
from focus groups, as well as barriers limiting its utility.

2. To conduct a preliminary RCT with 75 individuals with AUD utilizing disulfiram in early
recovery, comparing (a) Wisepill+SMS intervention, (b) monitoring by Wisepill only (i.e., no
SMS texts delivered), and (c) disulfiram use only (i.e., no Wisepill). The investigators
hypothesize: 2a. Relative to the Wisepill-only and disulfiram-only conditions, the
Wisepill+SMS condition will demonstrate improved outcomes with regard to the primary outcome
of interest (i.e., alcohol use), specifically greater percent days abstinent at end of
intervention (3-months) and at 6-month follow-up.

2b. Relative to the Wisepill-only and disulfiram-only conditions, the Wisepill+SMS condition
will result in greater adherence to medication, increased coping, increased self-efficacy,
and increased perceived social support.

2c. The investigators hypothesize that these mechanisms (i.e., medication adherence, coping
strategy utilization, abstinence self-efficacy, and perceived social support) will be
significantly associated with alcohol outcomes.

The investigators anticipate that this project will lead to the development of a
well-specified, novel, technology-supported medication adherence/relapse prevention
intervention for individuals with AUD utilizing disulfiram in early recovery that can be
subsequently tested in a future fully-powered randomized controlled treatment trial.

Inclusion Criteria:

- between 18 and 65 years of age

- meet DSM-5 criteria for an AUD, as assessed by the SCID-P,

- prescribed disulfiram while in the Alcohol and Drug Partial Hospital Program (i.e.,
while also meeting psychiatrist criteria for a disulfiram protocol)

- are currently enrolled in ADP

- has access to a phone capable of receiving SMS and access to email.

Exclusion Criteria:

- current DSM-5 diagnosis moderate/severe substance use disorder

- a history of psychotic disorder or current psychotic symptoms

- current suicidality or homicidality

- current use of an alcohol treatment medication other than disulfiram.